title: Two independent regions of simian virus 40 T antigen increase CBP/p300 levels, alter patterns of cellular histone acetylation, and immortalize primary cells.
abstract: Simian virus 40 (SV40) large T antigen (SVT) interferes with normal cell regulation and thus has been used to identify cellular components controlling proliferation and homeostasis. We have previously shown that SVT-mediated transformation requires interaction with the histone acetyltransferases (HATs) CBP/p300 and now report that the ectopic expression of SVT in several cell types in vivo and in vitro results in a significant increase in the steady-state levels of CBP/p300. Furthermore, SVT-expressing cells contain higher levels of acetylated CBP/p300, a modification that has been linked to increased HAT activity. Concomitantly, the acetylation levels of histone residues H3K56 and H4K12 are markedly increased in SVT-expressing cells. Other polyomavirus-encoded large T antigens also increase the levels of CBP/p300 and sustain a rise in the acetylation levels of H3K56 and H4K12. SVT does not affect the transcription of CBP/p300, but rather, alters their overall levels through increasing the loading of CBP/p300 mRNAs onto polysomes. Two distinct regions within SVT, one located in the amino terminus and one in the carboxy terminus, can independently alter both the levels of CBP/p300 and the loading of CBP/p300 transcripts onto polysomes. Within the amino-terminal fragment, a functional J domain is necessary for increasing CBP/p300 and specific histone acetylation levels, as well as for immortalizing primary cells. These studies uncover the action of polyomavirus T antigens on cellular CBP/p300 and suggest that additional mechanisms are used by T antigens to induce cell immortalization and transformation.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sáenz Robles
authors.forename: Chikdu
authors.initials: C
authors.lastname: Shivalila
authors.forename: Jeremy
authors.initials: J
authors.lastname: Wano
authors.forename: Shelly
authors.initials: S
authors.lastname: Sorrells
authors.forename: Alison
authors.initials: A
authors.lastname: Roos
authors.forename: James M
authors.initials: JM
authors.lastname: Pipas
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D027601:Polyomavirus Infections / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D013539:Simian virus 40 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014412:Tumor Virus Infections / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000821:virology
chemical_list: D000952:Antigens, Polyomavirus Transforming; D006657:Histones; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse